Cyclam-based compounds as a novel class of antibacterial and antitumoral agents

Abstract

Cyclams are macrocyclic polyamines which medical interest was fueled by the therapeutic potential of a bicyclam derivative in HIV infection, inflammatory diseases, cancer and stem-cell mobilization.[1] Taking advantage of the biocompatibility, the high metal chelation stability constants and the possibility of N-functionalization of the cyclam backbone, a variety of compounds have been explored in a wide range of medicinal applications.[2] The use of cyclams and cyclam-based complexes as antimicrobial and antitumoral agents has been described in recent years. In particular, trans-disubstituted cyclam salts revealed to be active antibacterial agents against both Gram-positive and Gram-negative bacteria.[3,4] In the field of anticancer applications, several attempts are being made, mostly with CuII complexes, envisaging their use as 64/67Cu radionuclides.[5] Recently, we found that trans-disubstituted cyclam derivatives and their CuII and FeIII complexes display relevant antitumoral activity against HeLa cancer cell lines.[6] To the best of our knowledge, this is the first report on an iron-cyclam compound tested as anticancer agent. [1] De Clercq, E., Nat. Rev. Drug Discov. 2003, 2, 581–587 [2] Liang, X.; Sadler, P. J., Chem. Soc. Rev. 2004, 33, 246-266 [3] Yu, M.; Nagalingam, G.; Ellis, S.; Martinez, E.; Sintchenko, V.; Spain, M.; Rutledge, P. J.; Todd, M. H.; Triccas, J. A., J. Med. Chem. 2016, 59, 5917–5921 [4] Alves, L. G.; Pinheiro, P. F.; Feliciano, J. R.; Dâmaso, D. P.; Leitao, J. H.; Martins, A. M., Int. J. Antimicrob. Agents 2017, 49, 646-649 [5] Cai, Z.; Anderson, C. J., J. Label. Compd. Radiopharm. 2014, 57, 224–230 [6] Pilon, A.; Lorenzo, J.; Rodriguez-Calado, S.; Adao, P.; Martins, A. M.; Valente, A.; Alves, L. G., ChemMedChem, 2019, 14, 770-778